Regional cerebral-blood flow (rCBF) and blood volume (rCBV) provide important information about local neuronal functional and cerebrovascular status. Positron-emission tomography (PET) and appropriate radiotracers permit non-invasive measurement of rCBF, but this technology has limited availability and is expensive. Recent development of fast magnetic resonance (MR) imaging techniques and FDA approved paramagnetic contrast agents may provide the means to measure rCBV and rCBF noninvasively, using widely available MR scanners. Quantitative determination of rCBV and rCBF using a paramagnetic contrast agent requires simultaneous measurement of both the arterial and the brain MR signal-time curves, with subsequent conversion into contrast-agent amounts. The goal of this project is to optimize and validate an MR method for the noninvasive measurement of rCBV and rCBF using standard MR hardware and intravenous IV-bolus injection of a paramagnetic contrast agent. The specific aims of this project are: 1) to measure the relationship between signal change and contrast-agent amount under in vitro conditions simulating the in vivo arterial MR signal-time curves to evaluate the effects of flow velocity and pulsatility, slice thickness, flip angle, and spatial resolution on the quantitative determination of the arterial input function. 2) to determine the effects of bolus width, temporal sampling, and reconstruction algorithm on the accuracy of the rCBV and rCBF estimates, in order to identify optimum data-collection parameters. Then for the optimal data-collection and reconstruction technique: 3) to determine the relationship between contrast-agent amount and change in T2 relaxation rate constant (deltaR2) in arterial blood, gray, and white matter in vivo using baboons. 4) to determine the reproducibility of in vivo MR imaging determinations of rCBV and rCBF for multiple injections as a function of bolus width and temporal sampling. 5) to compare rCBF values obtained using MR and radioactive microspheres in pigs. 6) to compare MR- and PET-derived values of rCBV and rCBF in (i) baboons under normal physiologic conditions, and (ii) in baboons under conditions of hyper- and hypocarbia. 7) to apply the techniques described in specific aim #2 above to the in vivo imaging data obtained on the baboons in specific aims #5 and #6 in order to determine the major sources of error, and the overall accuracy and sensitivity of this technique for determination of rCBV and rCBF. A fast, simple, noninvasive MR technique for measuring rCBV and rCBF on existing MR scanners without hardware modification would permit high- resolution recurrent determination of rCBV and rCBF in patients with neurological or psychiatric diseases, and in normal subjects for functional brain mapping studies.